Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22-82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In 'pure' grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age.

Summary:Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 ± 2.6%/mm Hg and 1.8 ± 1.3%/mm Hg, respectively, and those to hypocapnia were −3.5 ± 0.6%/mm Hg and −1.3 ± 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV ‫ס‬ 1.09 CBF 0.29 . The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, 64 Cu (half-life, 12.7 h) and 225 Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n 5 12; MIA PaCa-2, n 5 8). Tumor xenograft mice were investigated after the intravenous injection of 64 Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of 68 Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n 5 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, 225 Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n 5 6). Tumor size was monitored and compared with that of control mice (n 5 6). Results: Dynamic imaging of 64 Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of 64 Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for 64 Cu-FAPI-04 than for 68 Ga-FAPI-04, except in the heart, and excretion in the urine was higher for 68 Ga-FAPI-04 than for 64 Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. 225 Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that 64 Cu-FAPI-04 and 225 Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.

Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402-positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.

Background and Purpose-Echo-planar gradient-echo T2*-weighted MR imaging (GRE-EPI) may detect hypointense lesions representing microhemorrhages with high sensitivity. The aim of this study was to evaluate the effectiveness of GRE-EPI for detecting old lacunar hemorrhages in hypertensive patients with stroke. Methods-GRE-EPI was performed with a 1.5-T MRI system in 198 hypertensive patients with stroke (130 patients with hemorrhagic stroke and 68 patients with multiple lacunar stroke) and 66 age-matched healthy elderly individuals. Results-Concomitant hypointense foci were found in 84 (66%) patients with hemorrhagic stroke, 46 (68%) patients with multiple lacunar stroke, and 3 (5%) healthy elderly individuals. These hypointense foci were noted in the lentiform nucleus in 61 (47%) patients with hemorrhagic stroke, in the caudate nucleus in 9 (7%) patients, in the thalamus in 54 (42%) patients, in the corticosubcortical region in 57 (44%) patients, in the brain stem in 40 (34%) patients, and in the cerebellum in 32 (25%) patients. Key Words: cerebral hemorrhage Ⅲ echo-planar imaging Ⅲ hypertension Ⅲ lacunar infarction Ⅲ magnetic resonance imaging L acunar hemorrhages are defined as small intraparenchymal hematomas that result from the extravasation of blood and are often clinically silent. 1,2 Gradient-echo T 2 -weighted imaging (GRE) can depict old lacunar hemorrhages as areas of sharply defined hypointensity. [3][4][5][6][7][8][9][10][11] Hypertensive patients with spontaneous intracerebral hemorrhage are known to have concomitant silent foci of signal loss on GRE. [3][4][5][6] Multifocal hypointense cerebral lesions on GRE are associated with long-standing chronic hypertension, advancing age, lacunar infarction, and extensive white matter lesions. 8 -11 Fazekas et al 5 found multiple intracerebral foci of MR signal loss corresponding to focal hemosiderin deposits, with no evidence of other possible morphological abnormalities such as focal calcification or small vascular malformation, although the amount of hemosiderin deposition and the related field inhomogeneities were sometimes insufficient to be detected on GRE. 5 Echo-planar imaging (EPI), in which an entire image is obtained from a single radiofrequency pulse excitation, has become a routine MR technique. 12 An entire brain survey can be completed in as little as 2 seconds with the use of single-shot echo-planar gradient-echo T 2 -weighted imaging (GRE-EPI). GRE-EPI has sensitivity comparable to GRE in the detection of chronic hemorrhage. 13 GRE-EPI can visualize old lacunar hemorrhages as well-circumscribed areas of noticeable hypointensity. To our knowledge, however, there have been no large-scale studies on the prevalence and spatial distribution of old lacunar hemorrhages in hypertensive patients with stroke performed with GRE-EPI. The purpose of the present study was to detect foci of hypointensity in hypertensive patients with hemorrhagic or multiple lacunar stroke and to evaluate the effectiveness of GRE-EPI for the detection of old lacunar hemorr...

Prostate specific membrane antigen (PSMA)-ligand PET/CT is performed in patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. 18 F-PSMA-1007 is a promising PSMA-PET tracer based on clinical results, but detailed histologic confirmation has been lacking.

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI.

Hypercapnia and hypocapnia produce cerebral vasodilation and vasoconstriction, respectively. However, regional differences in the vascular response to changes in Paco2 in the human brain are not pronounced. In the current study, these regional differences were evaluated. In each of the 11 healthy subjects, cerebral blood flow (CBF) was measured using 15O-water and positron emission tomography at rest and during hypercapnia and hypocapnia. All CBF images were globally normalized for CBF and transformed into the standard brain anatomy. t values between rest and hypercapnia or hypocapnia conditions were calculated on a pixel-by-pixel basis. In the pons, cerebellum, thalamus, and putamen, significant relative hyperperfusion during hypercapnia was observed, indicating a large capacity for vasodilatation. In the pons and putamen, a significant relative hypoperfusion during hypocapnia, that is, a large capacity for vasoconstriction, was also observed, indicating marked vascular responsiveness. In the temporal, temporo-occipital, and occipital cortices, significant relative hypoperfusion during hypercapnia and significant relative hypoperfusion during hypocapnia were observed, indicating that cerebral vascular tone at rest might incline toward vasodilatation. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve by hypercapnia and in the correction of CBF measurements for variations in subjects' resting Paco2.